Platelet-rich plasma samples were exposed to shear stress in a specially designed rotational viscometer. Platelet response was characterized by the following measurements made before and after exposure to shear stress: platelet count, the level of 14C radiolabelled serotonin present in the plasma, the level of the platelet enzyme lactic dehydrogenase (LDH) present in the plasma, and the aggregation response to both exogenous ADP and collagen. The results show that preconditioning the platelets with aspirin caused a small reduction in shear-induced platelet aggregation, release, and lysis. Preconditioning the platelets with PGE1 and theophylline (in combination) or PGI2 and theophylline (in combination) caused a large reduction in shear-induced platelet aggregation, but caused a large increase in the shear-induced release of LDH and serotonin. It is concluded that aspirin provides a small amount of protection of the platelets from the effects of shear stress. Prostaglandin greatly reduced shear-induced platelet aggregation, while simultaneously rendering the plateletes more susceptible to shear-induced lysis.